RE1-silencing transcription factor

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RE1-silencing transcription factor
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols REST ; NRSF; XBR
External IDs OMIM600571 MGI104897 HomoloGene4099 GeneCards: REST Gene
RNA expression pattern
PBB GE REST 212920 at tn.png
PBB GE REST 204535 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5978 19712
Ensembl ENSG00000084093 ENSMUSG00000029249
UniProt Q13127 Q8VIG1
RefSeq (mRNA) NM_001193508 NM_011263
RefSeq (protein) NP_001180437 NP_035393
Location (UCSC) Chr 4:
57.77 – 57.8 Mb
Chr 5:
77.27 – 77.29 Mb
PubMed search [1] [2]

RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST gene, and acts as a transcriptional repressor.[1][2][3] REST is expressly involved in the repression of neural genes in non-neuronal cells.[4][3] Many genetic disorders have been tied to alterations in the REST expression pattern, including colon and small-cell lung carcinomas found with truncated versions of REST.[5] In addition to these cancers, defects in REST have also been attributed a role in Huntington Disease, neuroblastomas, and the effects of epileptic seizures and ischaemia.

Function[edit]

This gene encodes a transcriptional repressor which represses neuronal genes in non-neuronal tissues. It is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element (NRSE, also known as RE1). The protein is also found in undifferentiated neuronal progenitor cells, and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described; however, their full length nature has not been determined.[1] REST is found to be down-regulated in elderly people with Alzheimer's disease.[6]

REST contains 8 Cys2His2 zinc fingers and mediates gene repression by recruiting several chromatin-modifying enzymes.[7]


NRSF bound to DNA and cofactors on each of its two cofactor binding domains. 
Chromatin remodeling occurs, causing the gene to be 'turned off'. 

Interesting to note that REST strongly correlate with increased longevity. REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity.[8]

Interactions[edit]

RE1-silencing transcription factor has been shown to interact with RCOR1.[9]

References[edit]

  1. ^ a b "Entrez Gene: REST RE1-silencing transcription factor". 
  2. ^ Schoenherr CJ, Anderson DJ (March 1995). "The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes". Science 267 (5202): 1360–3. doi:10.1126/science.7871435. PMID 7871435. 
  3. ^ a b Chong JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G (March 1995). "REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons". Cell 80 (6): 949–57. doi:10.1016/0092-8674(95)90298-8. PMID 7697725. 
  4. ^ Coulson J.M. (September 2005). "Transcriptional Regulation: Cancer, Neurons and the REST". Current Biology 15 (17): R665–R668. doi:10.1016/j.cub.2005.08.032. 
  5. ^ Westbrook TF, Martin ES, Schlabach MR, Leng YM, Liang AC, Feng B, Zhao JJ, Roberts TM, Mandel G, Hannon GJ, DePinho RA, Chin L, Elledge SJ (June 2005). "A Genetic Screen for Candidate Tumor Suppressors Identifies REST". Cell 121 (6): 837–848. doi:10.1016/j.cell.2005.03.033. 
  6. ^ Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A. (2014). "REST and stress resistance in ageing and Alzheimer's disease". Nature. doi:10.1038/nature13163.  edit
  7. ^ Ooi L, Wood IC (July 2007). "Chromatin crosstalk in development and disease: lessons from REST". Nat. Rev. Genet. 8 (7): 544–54. doi:10.1038/nrg2100. PMID 17572692. 
  8. ^ Tao Lu, Liviu Aron, Joseph Zullo, Ying Pan, Haeyoung Kim, Yiwen Chen, Tun-Hsiang Yang, Hyun-Min Kim, Derek Drake, X. Shirley Liu, David A. Bennett, Monica P. Colaiácovo, Bruce A. Yankner.(2014). REST and stress resistance in ageing and Alzheimer’s disease. Nature, doi: 10.1038/nature13163
  9. ^ Andrés ME, Burger C, Peral-Rubio MJ, Battaglioli E, Anderson ME, Grimes J, Dallman J, Ballas N, Mandel G (August 1999). "CoREST: a functional corepressor required for regulation of neural-specific gene expression". Proc. Natl. Acad. Sci. U.S.A. 96 (17): 9873–8. doi:10.1073/pnas.96.17.9873. PMC 22303. PMID 10449787. 


Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.